This grant application defines the anticipated research undertakings of the principal investigator which will be coordinated in program fashion with the activities of other investigators who enjoy expertise in pathology, biochemistry, physiology, biophysics and gastroenterolgy. The major objective of the program is to systemically evaluate alterations of calcium and phosphate and bone mineral metabolism in chronic hepatic or renal (glomerular or tubular) disorders and those hormones (vitamin D and PTH) essential for homeostatic regulation. The application represents a consolidation of all ongoing and anticipated research in this area some of which was previously funded by an NIH contractual agreement. With the combined expertise of all investigators we plan to achieve a better and more correlated understanding of the in vivo metabolism of vitamin D and its metabolites in acidotic and uremic disorders and hepatic insufficient states characterized by parenchymal destruction with and without hyperbilirubinemia. Isolation and purification of rat and human intestinal calcium binding protein(s) will proceed concurrently with other studies defining the relationship between intestinal calcium and phosphate transport, vitamin D activity and intestinal protein synthesis. Factors which initiate or retard dialysis bone disease in the experimental animal will be evaluated and the relationship between bone mineralization and resorption and carbohydrate metabolism explored. Investigations are also proposed for evaluating vitamin D-regulated phosphate transport in the isolated mammalian renal tubule preparation and the absorption and excretion of calcium and phosphorus in a mouse animal model of human x-linked hypophosphatemic syndromes.